MXPA97003338A - Asept transfer - Google Patents

Abstract

The present invention relates to a method for aseptic and automatic transfer of unsealed pharmaceutical containers, which have been aseptically filled with a pharmaceutical preparation, from a filling device, to a subsequent unit, the method is characterized by the steps of: a ) introduce an inert, sterile protective gas into a transportable chamber, b) insert the chamber into the filling device, c) introduce the pharmaceutical containers into the chamber and close the chamber, and d) transport the chamber to the subsequent unit, in in which the pharmaceutical containers are removed from the chamber, the protective gas is distributed continuously and regularly in steps b) -d) over the pharmaceutical containers without sealing

Description

AN EEDENTS OF THE INVENTION The present invention relates to a method and device for aseptic and automatic transfer of unsealed pharmaceutical containers, which have been aseptically filled with a pharmaceutical preparation, from a filling device to a subsequent unit. With regard to pharmaceutical formulations, it has always been a serious problem to maintain the hygienic conditions required during the transfer of solutions or substances aseptically filled in pharmaceutical containers from a filling machine to a subsequent process step, for example, a step of lyophilization. During such a transfer, hygienic conditions should always be the same as during the filling and lyophilization process. In addition, the authorities, in all likelihood, will be stricter with respect to the requirements of higher purity levels in this technical area.

REF: 24599 DESCRIPTION OF THE PREVIOUS TECHNIQUE It is known to manually transfer trays with unsealed or partially sealed containers, aseptically filled with pharmaceutical preparations from a filling machine to a lyophilizer. In such a case, the pharmaceutical preparation in the container is exposed to the surrounding air and the particles and microorganisms therein, whereby the hygiene class of the preparation is adversely affected. Air-sensitive preparations are difficult to handle in such a manner. In an automatic transfer process, it is also known to use a large shelf and filter sterilized air as a protective gas. However, the equipment required for such use requires a very large amount of space, and the time required is very long and therefore harmful for the preparation. EP 440 042 (Capsulite Spa) relates to a process and device for the sterilization of plants for filling, for example, pharmaceutical bottles by the use of injection of a nitrogen system. The purpose of this device is to clean the filling plant at the end of a production cycle and maintain a pressure with inert gas in it until the subsequent production cycle begins. The injection of nitrogen is a complement to the injection of water to clean and steam. JP 03216174 (Iwatani International Corp.) relates to an aseptic freezing device, in which liquid nitrogen is used to freeze a pharmaceutical product. The liquid nitrogen is passed through a filter in the freezing chamber, so that microorganisms and dust are separated. The cleaned nitrogen is used to freeze the product. However, there is still a need for a process for aseptic transfer of aseptically filled pharmaceutical containers, which allows for a higher hygiene class to be maintained during the transfer process and which requires a relatively small space.

BRIEF DESCRIPTION OF PE TO XNV? NCT.QN The object of the present invention is to eliminate the problems mentioned above. This objective is obtained by a method which is of the type described by way of introduction and which is characterized by the steps of: a) introducing an inert protective gas, sterile, into a transportable chamber, b) inserting the camera into the device filling, c) introducing the pharmaceutical containers in the chamber and closing the chamber, and d) transporting the chamber to the subsequent unit, in which the pharmaceutical containers are removed from the chamber, the protective gas is distributed continuously and regularly in Steps b) -d) on unsealed pharmaceutical containers. The object of the invention is also obtained by a transfer device for aseptic and automatic transfer of unsealed pharmaceutical containers, which have been aseptically filled with a pharmaceutical preparation, from a filling device to a subsequent unit, the transfer device comprises a controllable transport vehicle, a vertically adjustable platform provided thereon and a hermetically sealed and transportable chamber which is provided on the platform and which supports the pharmaceutical containers during transfer, the transfer device is characterized in that the chamber comprises: a) an upper part provided with a protective gas inlet, b) a lower part provided with a frame for holding the pharmaceutical containers during the transfer and with an opening that can be closed for the introduction and removal of pharmaceutical containers, the upper part and the lower part are separated by an intermediate flow distributor, substantially horizontal, for a regular distribution of protective gas from the top, on the containers pharma in the lower part. The present invention is advantageous insofar as it allows an improved transfer of the filled pharmaceutical containers, which is performed aseptically and at the same time maintains the required hygienic class. In addition, the total costs of equipment for the transfer process are less than for a static process, and the workload of the operators is minimized. Another advantage is that several subsequent units can be serviced, for example, lyophilizers. None of the aforementioned references mentions a method for automatic and aseptic transfer by the use of a protective gas distributed in a regular manner on containers aseptically filled in a transportable chamber.

The present invention will now be described in more detail with reference to the accompanying drawings, in which: Figure 1 is a cross-sectional view of a chamber used in the process according to the invention, and Figure 2 is a view in cross section of a transport device of the invention, in operation.

DESCRIPTION OF A MODALITY With reference to Figure 1, the transfer device according to the invention comprises a transportable chamber 1 which is sealable and has an upper part 8 provided with a protective gas inlet 7 and which acts as a pressure equalizing space, as well as a lower part 9 provided with a frame 13 for holding the pharmaceutical containers 2 during the transfer thereof. In addition, the lower part 9 is provided with a closable opening 14 for the introduction and removal of the pharmaceutical containers 2. The lower part of the lower part 9 is also provided with grooves (not shown) for the protective effluent gas in order to allow the continuous introduction of the protective gas into the chamber 1, and in this way avoid overpressure therein. The upper part 8 and the lower part 9 are separated by an intermediate flow distributor 10, substantially horizontal, which allows the regular introduction of the protective gas 3 from the upper part 8 onto the holes of the pharmaceutical containers 2 in the lower part 9. The flow distributor 10 comprises perforated plates and a filter interposed therebetween. The flow distributor 10 serves to distribute the flow of the protective gas in a regular manner over the entire area of the lower part 9, in which the containers 2 are located. This is obtained by reducing the pressure obtained in the flow distributor 10. . Preferably, the entire chamber 1 is sterilized, for example, by an autoclave, before use. At the bottom of the lower part 9, there is also provided a pull device controlled by ball screws (not shown) for the introduction and removal of the containers 2 and from the chamber 1. The frame 13, which is also located at the bottom of the lower part 9 and connected to the pulling device, it is adapted to maintain the number of containers 2 required during the transfer. The number of containers 2 to be transferred depends for example on the type of pharmaceutical container 2 that is considered. In one embodiment of the present invention, 400 bottles (vials) are maintained by the frame 13 during the transfer. When liquid preparations are also to be transferred, it is very important to keep the surface of the preparation as motionless as possible, since all types of splashing should be avoided. Preferably, a closing opening 14 of the chamber 1 is located in one of the side walls of the lower part 9. The opening 14 can be opened and closed by means of a door. The protective gas 3 is sterilized by filtration, for example, with the aid of a particulate filter, before being introduced into the upper part 8 of the chamber 1. The protective gas 3 can be continuously introduced from the protective gas supply connected to the chamber 1. Preferably, the protective gas 3 is inserted vertically through an opening in the upper part of the upper part 8. The protective gas 3 is preferably nitrogen, a noble gas or a mixture thereof. In a preferred embodiment, nitrogen is used as the protective gas.

The filter of the flow distributor 10 is a commercially available PPM-PPF filter, made of sintered plastic spheres having an average diameter of about 3 mm. The filter capacity is approximately 3.5 particles per liter (100 particles per cubic foot). However, other filters with similar capacity and construction can also be used. The pharmaceutical containers 2 to be transferred from the filling device 6 to the subsequent unit 4 according to the method of the invention are preferably pharmaceutical vials or vials., ampoules or bottles or other similar pharmaceutical containers. The containers 2 can be made of any suitable conventional material, but are usually made of glass or plastic. In addition, the containers 2 remain unsealed after the filling operation. By the expression "unsealed" as used throughout the description and the claims, it is meant that the preparation in each container 2 is in contact with the surrounding atmosphere. However, the containers 2 can be provided with conventional caps of different shapes in such a way that the containers 2 are partially sealed.

When the subsequent unit 4 is a lyophilizer, the containers 2 can be provided with a stopper having openings located horizontally in relation to the transfer direction to allow evaporation of vapor and / or gaseous components of the pharmaceutical product in the subsequent lyophilization stage. . After such evaporation, the containers 2 holding the lyophilized pharmaceutical preparation 5 are hermetically sealed. The pharmaceutical preparation 5 in unsealed containers 2 is transferred aseptically and can be a liquid or solid preparation. In a preferred embodiment, the pharmaceutical preparation is a solution of omeprazole, which is sensitive to carbon dioxide. . By the term "filled" or "filled" used throughout the description and the claims, it is meant that the pharmaceutical preparation has been added to the container 2 in the filling device to an optional level in container 2. The dimensions of the chamber 1 are not critical, but it is important that there is sufficient space between the orifices of the container and the flow distributor 10 in the lower part 9. Additionally, the containers 2 and the preparation do not necessarily have to be pharmaceutical. Others - II - types of containers filled with liquid or solid chemical preparations that require transfer or storage conditions that are hygienic or non-oxidizable, can also be treated by the process according to the present invention. With reference to Figure 2, the transfer device constituted of the camera 1 also includes a controllable transport vehicle 11 and a vertically adjustable platform 12, provided thereon. The chamber 1, in turn, is provided on the platform 12 and is transferred from the filling device 6 to the subsequent unit 4, which preferably consists of one or more lyophilizers. The transport vehicle 11 is preferably a mini-truck controlled by a laser-guided control system, which controls the minicarretilla in the operation area thereof. The control signals are transferred by radio link, and the system considerably facilitates changes in the movement pattern of the minicarretilla. The total process time for the transfer is less than 20 minutes, preferably about 2.5 minutes.

Now the present invention will be discussed with the help of the following example of a transfer process for omeprazole.

EXAMPLE In a transfer room, two minicarretillas are operated simultaneously, each one has a chamber 1 for the transport of the containers 2. The chamber has a length of 0.75, a width of 0.4 m and a height of 0.35 m. The height of the upper part 8 is 0.15 m and the height of the lower part is 0.20 m. The total thickness of the perforated plates and the PPM-PPF filter interposed between them is 1 cm. The perforated plates have a thickness of 1 mm, respectively, and are made of stainless steel. The total diameter of the same is 3 mm placed in a triangle with a width of 5 mm. After filling with nitrogen, each chamber 1 is inserted in two different places at the same height level in the filling machine. We introduce 400 pharmaceutical vials or vials with an inner diameter of 21 mm and a height of 45 mm, which have been filled aseptically with a solution of omeprazole, up to a degree of approximately 25% of the bottle and are provided with partially sealed caps, which are introduced through the opening 14 in each chamber 1, which is then closed and transported by the minicarretilla while nitrogen 3 is continuously introduced therein at a flow rate of approximately 500 1 / min. The chambers 1 are transferred to three different freeze dryers, each consisting of 144 positions arranged in 12 shelf levels with three width positions and four length positions in each level. The vertically adjustable platform 12 is guided by the program control system of the mini-carts to insert the bottles 2 in correct positions in the lyophilizer 4. The bottles 2 are removed from chamber 1 to the freeze dryer, even under the aseptic conditions required. Therefore, the entire transfer of the containers 2 from the filling machine 6 to the subsequent freeze dryer is carried out completely automatically and under the required hygiene conditions. The total time of the process is approximately 2.5 minutes.

It is noted that in relation to this date, the best method known by the applicant to carry out the aforementioned invention, is the conventional one for the manufacture of the objects to which it relates. Having described the invention as above, property is claimed as contained in the following:

Claims (11)

1. A method for aseptic and automatic transfer of unsealed pharmaceutical containers, which have been aseptically filled with a pharmaceutical preparation, from a filling device, to a subsequent unit, the method is characterized by the steps of: a) introducing a protective gas inert, sterile, in a transportable chamber, b) insert the chamber in the filling device, c) introduce the pharmaceutical containers in the chamber and close the chamber, and d) transport the chamber to the subsequent unit, in which the pharmaceutical containers they are removed from the chamber, the protective gas is continuously and regularly distributed in steps b) -d) over unsealed pharmaceutical containers.

2. The method according to claim 1, characterized in that a noble gas or a mixture thereof is introduced as a protective gas into the chamber.

3. The method according to claim 1, characterized in that flasks or vials, ampoules or bottles filled with the pharmaceutical preparations are transferred aseptically to the subsequent unit.

. The method according to claim 3, characterized in that the pharmaceutical bottles contain a solution of omeprazole and are transferred aseptically to the subsequent unit.

5. The method according to claim 1, characterized in that the pharmaceutical containers are transferred aseptically to at least one lyophilizer.

6. The method according to claim 1, characterized in that the chamber is sterilized by filtration before use.

7. The transfer device for aseptic and automatic transfer of unsealed pharmaceutical containers, which has been aseptically filled with a pharmaceutical preparation from a filling device to a subsequent unit, the transfer device comprises a transport vehicle, a vertically adjustable platform provided on it and a transportable and sealable chamber provided on the platform and which holds the pharmaceutical containers during the transfer, characterized in that the chamber comprises: a) an upper part provided with a protective gas inlet, b) a lower part provided with a frame for holding the pharmaceutical containers during the transfer and with a resealable opening for the introduction and removal of the pharmaceutical containers, the upper part and the lower part are separated by an intermediate flow distributor, substantially horizontal; al, for regular distribution of protective gas from the top over the pharmaceutical containers in the lower part.

8. The transfer device according to claim 7, characterized in that the flow distributor of the chamber comprises perforated plates and a filter made of sintered plastic spheres interposed therebetween.

9. The transfer device according to claim 7, characterized in that the frame of the chamber is capable of holding approximately 400 pharmaceutical containers during the transfer.

10. The transfer device according to claim 7, characterized in that the transfer of the pharmaceutical containers in the chamber is controlled by a laser-guided control system for the transport vehicle.

11. An aseptic pharmaceutical container, treated in accordance with the method of claim 1.